An illustration of human pregnancy and directions of the placenta blood flow. The right panel shows the relationship of the uterus, placenta, and fetus during pregnancy. The left panel shows the directions of blood flow from mother to the placenta and (more. )
2.1. Maternal-placental blood circulation
Uteroplacental circulation is not fully established until the end of the first trimester. Although the exact mechanism of how the uteroplacental circulation is established is not completely understood, two theories have been proposed. The first theory is that in the first trimester, endovascular trophoblasts migrate along the decidual spiral arteries, invade the vessel walls, and create a path for maternal blood to perfuse the placenta intervillous space. This theory is supported by the presence of endovascular trophoblasts in the decidual spiral arteries of the first trimester placenta [4 ,5 ]. The second theory proposes that trophoblasts invade decidual spiral arteries and form trophoblastic plugs. These trophoblastic plugs obstruct maternal blood flow into the intervillous space and prevent flow until the end of first trimester of pregnancy (10–12 weeks). The plugs then loosen and permit continuous maternal blood flow into the intervillous space. This theory is based on the observations of ex vivo histologic analysis of hysterectomy specimens of first-trimester placentas, in which plugs of trophoblasts were found either partially or fully obstructing or filling the vessel lumen of decidual spiral arteries [6 ]. Although the two theories diverge as to whether or not invading trophoblasts ‘plug’ the arteries to prevent blood flow into the intervillous space, it is clear that the genesis of uteroplacental (maternal-placental) blood flow during the first trimester is a dynamic and progressive process.
Normal early placental development results in transformation of spiral arteries that extend from the decidua (the layer of tissue lining the uterus) to the muscle layer. Most textbooks provide the classic description of the placenta circulation based on studies of second-, or third-trimester placentas. As shown in Figure 2.2. maternal blood enters the placenta through the basal plate endometrial arteries (spiral arteries), perfuses intervillous spaces, and flows around the villi where exchange of oxygen and nutrients occurs with fetal blood. It has been estimated that there are about 120 spiral arterial entries into the intervillous space at term [7 ]. Maternal blood traverses through the placenta intervillous space and drains back through venous orifices in the basal plate, then returns the maternal systemic circulation via uterine veins. Maternal-placental blood flow is propelled by maternal arterial pressure because of the unique nature of low-resistance uteroplacental vessels, which accommodate the massive increase in uterine perfusion over the course of gestation [7 ]. During pregnancy, maternal blood volume increases progressively from 6–8 weeks of gestation and reaches a maximum approximately at 32–34 weeks and then keeps relatively constant until term. In general, maternal blood (plasma) volume is increased up to 40–50% near term compared to the nonpregnant state. Gowland et al. studied maternal blood perfusion in human placenta from 20 weeks of gestational age until term using echo planar imaging (EPI) [8 ]. They found that in normal pregnancies the average perfusion rate was about 176 ± 24 ml/100 gram/minute.
A schematic drawing of a section through a full–term placenta. Upper panel: (1) The relation of the villous chorion (C) to the decidua basalis (D) and the fetal-placental circulation; (2) The maternal blood flows into the intervillous spaces in (more. )
Spiral artery remodeling : Remodeling of the uterine arteries is a key event in early pregnancy that begins after implantation. The trophoblast differentiates into villous trophoblasts and extravillous trophoblasts. These trophoblasts have distinct functions when in contact with maternal tissues. Villous trophoblasts give rise to the chorionic villi, the major structure of placental cotyledon. Chorionic villi primarily transport oxygen and nutrients between fetus and mother. Extravillous trophoblasts migrate into the decidua and myometrium and penetrate the maternal vasculature. The extravillous trophoblasts can be classified as interstitial trophoblasts and endovascular trophoblasts. Interstitial trophoblasts invade the decidua and surround spiral arteries. Endovascular trophoblasts invade spiral arteries. In the uterine spiral arteries, endovascular trophoblasts interdigitate between the endothelial cells, replacing the endothelial lining and most of the musculoelastic tissue in the vessel walls, thereby creating a high-flow, low-resistance placental circulation. “High flow and low resistance” is the description usually given for the normal uteroplacental vasculature as a result of physiological remodeling of decidual spiral arteries. Figure 2.3 illustrates the process of spiral artery remodeling during pregnancy.
The process of spiral artery remodeling during pregnancy. In early pregnancy, two types of extravillous trophoblasts are found outside the villous, endovascular and interstitial trophoblasts. Endovascular trophoblasts invade and transform spiral arteries (more. )
Placental blood flow is increased throughout pregnancy. The volume of placental blood flow is about 600–700 ml/minute (80% of the uterine perfusion) at term. Steep falls in the pressure occur in the transition from uterine arteries to intervillous spaces. The pressure is about 80–100 mmHg in uterine arteries, 70 mmHg in spiral arteries, and only 10 mmHg within intervillous space. The low-resistance of uteroplacental vessels and the gradient of blood pressure between uterine arteries and placental intervillous space allow the maternal blood to perfuse the intervillous space efficiently and effectively. The blood in the intervillous space is therefore completely exchanged two to three times per minute. In general, the spiral arteries are perpendicular to the uterine wall, while the veins are parallel to the uterine wall. This arrangement facilitates closure of the veins during uterine contractions and prevents squeezing of maternal blood from the intervillous space.
2.2. Fetal-placental circulation
Umbilical cord: The umbilical cord is the lifeline that attaches the placenta to the fetus. During prenatal development, the umbilical cord comes from the same zygote as the fetus. The umbilical cord in a full-term human neonate averages
50–70 centimeters (20 inches) long and
(0.75 inches) in diameter. It extends from the fetal umbilicus to the fetal surface of the placenta or chorionic plates. The cord is not directly connected to the mother’s circulatory system. Instead it joins the placenta, which transfers materials to and from the mother’s blood without allowing direct mixing. The umbilical cord contains one vein (the umbilical vein) and two arteries (the umbilical arteries) buried within Wharton’s jelly. The umbilical vein carries oxygenated, nutrient-rich blood from the placenta to the fetus, and the umbilical arteries carry deoxygenated, nutrient-depleted blood from the fetus to the placenta (Figure 2.2 ). Any impairment in blood flow within the cord can be a catastrophic event for the fetus.
Umbilical vessels are sensitive to various vasoactivators, such as serotonin, angiotensin II, and oxytocin. The contractility of smooth muscles in vessel walls is also influenced by substances produced by the neighboring endothelial cells in a paracrine manner [9 ]. Umbilical cord vessels produce several potent vasodilators. For example, an in vitro study has shown that the endothelium from umbilical vein (HUVECs) produces far more prostaglandins than the endothelium from umbilical arteries (HUAECs) [10 ]. Interestingly, the synthesis and production of prostacyclin (PGI2 ) and PGE2 are significantly less by HUVECs from smoking and diabetic pregnant women than in normal pregnant women [11 ]. Both PGI2 and PGE2 are potent vasodilators and inhibitors for platelet aggregation. Nitric oxide (NO) and atrial natriuretic peptide (ANP) are also present in umbilical vessels. Giles et al. studied the correlation of nitric oxide synthase (NOS) activity in placentas with Doppler ultrasound umbilical artery flow velocity wave-forms. They found that placentas from women with abnormal umbilical artery flow velocity waveforms showed significantly lower mean NOS activity than did placentas from women with normal umbilical artery flow velocity wave-forms .
Placental villous capillaries: At the junction of umbilical cord and placenta, the umbilical arteries branch to form chorionic arteries and traverse the fetal surface of the placenta in the chorionic plate and branch further before they enter into the villi. The chorionic arteries are easily recognized because they always cross over the chorionic veins. These vessels are responsive to vasoactive substances as mentioned above. About two thirds of the chorionic arteries form networks supplying the cotyledons in a pattern of disperse-type branching. The rest of the chorionic arteries radiate to the edge of the placenta and down to a network. Figure 2.4 shows the maternal and fetal surfaces of a placenta; note the disperse-type branching pattern of fetal vessels (fetal surface) in the chorionic plate.
Maternal and fetal surface of the placenta. Please note the pattern of disperse-type branching of fetal vessels (fetal surface) in the chorionic plate. (From http://www.walgreens.com/marketing/library/graphics//images/en/17010.jpg). Used with permission (more. )
Each umbilical cord artery generally provides eight or more terminal chorionic plate arteries, which are referred to as stem arteries of the peripheral trunci chorii to the fetal villous cytyledons. The first order branches have an average length of 5–10 mm; the artery is an average of 1.5 mm in diameter with the accompanying vein being about 2 mm. These truncal vessels divide into four to eight horizontal cotyledonary vessels of the secondary order, with an average diameter of 1 mm. The horizontal distance varies with the size of the cotyledon, and as they curve toward the basal plate, they begin branching into the third-order villous branches. There are about 30–60 branches in each cotyledon, with calibers of 0.1–0.6 mm and lengths of 15–25 mm. In the villi, the third-order villous branches form an extensive arteriocapillary venous system, villous capillaries . bringing the fetal blood extremely close to the maternal blood; but no intermingling between fetal and maternal blood occurs. There are about 15–28 cotyledons per placenta.
The villous capillaries are branches of the umbilical vessels, and the capillary networks are the functional unit of maternal-fetal exchange. The blood pressure in the umbilical arteries averages about 50 mmHg, and the blood flows through smaller vessels that penetrate the chorionic plate to the capillaries in the villi where arterial blood pressure falls to 30 mmHg. In the umbilical vein the pressure is 20 mmHg. The pressure in the fetal vessels and their villous branches is always greater than that within the intervillous space. This protects the fetal vessels against collapse.
Assessment of fetal blood flow : Ultrasound and Doppler flow measurements provide means to visualize the umbilical cord and to evaluate the fetal blood flow. Figure 2.5 shows an example of an ultrasound color image of umbilical cord arteries and vein. By measuring the amount of forward blood flow through the umbilical artery during both fetal systole and diastole, an overall measure of fetal health can be obtained. In general, the more forward blood flow from the fetus to the placenta through the umbilical artery, the healthier the fetus. Table 2.1 summarizes measurements and vessel blood flow characteristics accessed by ultrasound and Doppler devices. The mean absolute vein blood flow is about 443 ± 92 ml/min in normal umbilical cord between 24 and 29 weeks of gestation, and reduced absolute vein blood flow is associated with low fetal birthweight [13 ]. Therefore, an assessment of fetal blood flow through the umbilical cord by ultrasound color Doppler sonography has proven to be a valuable noninvasive procedure for assessing fetal well-being during pregnancy.
Ultrasound color imaging of umbilical cord arteries and vein. Red: umbilical cord vein; and blue: umbilical cord arteries. (from http://www.medical.siemens.com). Image courtesy of Siemens Healthcare.
A list of parameters of umbilical cord measurements and vessel blood flow characteristics accessed by Ultrasound .
Chorionic plates arteries and veins branch from the umbilical cord insertion. A: Chorionic plate of a normal term placenta; B: umbilical cord insertion in the margin of the placenta; and C: extra lobe present with a velamentous vessel connecting. Asterisks (more. )